The long-term objectives of the studies proposed in this application are to define the roles of various classes of antibodies in the induction of immunologically mediated tissue damage and to devise procedures for the selective stimulation of individual classes of antibodies in response to cell surface antigens. This information will be obtained through the use of transplanted tissues as targets for potentially destructive or protective antibodies. We plan also to study the mechanisms involved in antibody-mediated destruction or protection (enhancement) and to investigate the genetic determinants of responsiveness insofar as they involve differences in the kinds of antibodies formed in response to cell surface antigens.